Prevention of hypertensive vasculopathy by nifedipine in salt-loaded Dahl rats.

In female "salt-sensitive" (S) Dahl rats, with hypertension induced by 8% sodium chloride (NaCl) in the diet for six weeks, a severe generalized arteriopathy was observed histopathologically. Fibrinoid degeneration, medial hyperplasia and periarteritis were especially pronounced in the preglomerular arterial system of the kidneys. Necrosis of afferent glomerular arterioles led to regressive changes in the renal corpuscles. Numerous dilated renal tubules were filled with protein casts. In the heart, arterial lesions were predominantly localized in the outer wall of the right ventricle. Occlusion of intracardiac arteries was accompanied by focal myocardial necrosis and fibrous replacement of the myocardial fibres. A left ventricular hypertrophy was found. The degree of renal arteriopathy inversely correlated with the magnitude of the hematocrit. S rats treated with nifedipine, 300 ppm in addition to 8% NaCl in the diet remained normotensive. No changes in vessels, tissues or in the hematocrit were seen in any of the nifedipine-treated rats. The same picture was observed in "salt-resistant" (R) rats on a high (8%) and on a low (0.4%) NaCl diet. S rats fed a low NaCl diet showed only dilated renal tubules containing protein casts. It is assumed that nifedipine primarily decreases the renovascular resistance in S rats under salt load, enabling the kidney to eliminate excess sodium without inducing pressure natriuresis. Organ damage in salt-loaded S rats is thus due to a fulminant increase in blood pressure, compensating for the sluggish natriuresis.